At
a time when DNA databases are sprouting up like mushrooms, Estonia wants
to enter the competitive market for gene hunting in a unique way. It will
be a matter of give and take in this tiny Baltic country. The state will
ask donors for health information and DNA, but in return, and unlike any
existing genetic database, Estonian citizens will be allowed to later
access their own genetic profiles.

Panoramic scene of Tallin, the captial
city of Estonia.

The Estonian gene bank and health database would be the world's largest.
The aim is to include genetic profiles and information on individual health
status and lifestyle from 75 percent of the 1.4 million citizens. Developed
by a group of scientists of the Estonian Genome Foundation (EGF), the
project was first presented to politicians and the public a year ago.
Now there are three big steps ahead of them: getting legislation in place,
running a pilot project, and finally building the gigantic gene bank.
With enthusiasm in both government and opposition, Eiki Nestor, Minister
of Social Affairs, expects a law governing the database and research on
human genetics to be passed by the parliament before Christmas.

"Thinking ahead, our database could benefit individual donors directly,"
says Andres Metspalu, the head of molecular diagnostics at the University
of Tartu, who originated the idea of a national gene bank. And what he
is thinking of is the future's predictive and individualized medicine.
As researchers identify still more genetic variations that cause disease
or confer disease risk, a donor could readily request his or her status
for a given genebe it related to heart disease, Alzheimer's or other
conditionsand seek preventive care. The door also opens on effectively
stratifying drug treatment on a nation-wide scale, as medicine tailored
to individual genotypes becomes reality. Trustee of the Merck Genome Research
Institute Thomas Caskey notes that "this could be a model for other countries
to follow," and adds that the potential for an economic return for the
health care system is substantial.

There is also the scientific return. The Estonian database could be an
important tool for identifying disease genes by way of linking and mining
its health data and DNA profiles, which would be coded for researchers.
There is a particular focus on genes involved in common diseases such
as cancer, diabetes, and heart disease and the Estonians may well deliver.
Earlier, isolated and genetically homogeneous populationssuch as
the Basque or the Icelanderswere touted as ideal for gene hunting
but there is a growing consensus that heterogeneity may be an advantage
in complex conditions involving many genes and environmental factors.
Population size also matters, explains medical statistician Max Baur of
the University of Bonn, Germany. "In many disease models a very large
sample of people will be necessary to home in on genes that play a relatively
weak role," he says. Baur also points out that it will be critical to
compare study results across various populations.

"With the human genome fully mapped we need population data banks to
understand gene function, and we must build an ethics standard for population
studies," says Bartha Maria Knoppers, chairwoman of the Human Genome Project's
Ethical, Legal & Social Issues Evaluation Committee. She considers the
Estonian proposal for individual data access the more responsible approach
but underlines the ethical requirement to educate the general public in
understanding genetic information.

Flag of Estonia

"We want to do this right and make sure the project doesn't run into
problems later," says EGF chairman Jaanus Pikani who is involved in launching
a massive educational program on genetics directed at the public. This
leads up to a pilot project in which 10,000 volunteers are recruited by
their physicians to answer extensive health questionnaires and give blood
for later genotyping. With a positive outcome, Pikani predicts the major
effort can begin within a year and one million people will be sampled
over a five-year period. The health database will evolve as donors' medical
information is entered continually. Genotyping will be done using tens
of thousands of single nucleotide polymorphisms or SNP markers, which
are single DNA base alterations narrowly spaced over the genome.

The potentially explosive idea of collecting and storing a nation's health
data and genetic profiles have elicited little discussion in Estonia.
"We should have more public debate about such an important development,"
says Pikani and he hopes to get things moving as the educational program
rolls out TV specials and call-ins with live discussions. The most vocal
critic of the database plan has been cancer specialist Tiina Tasmuth of
the Estonian Christian Physicians' Society. She is outraged that significant
government funds would go into high-tech approaches with long term aims
when Estonia needs to improve the basic standard of its all-public health
care system.

"We need to do both, and I believe this project will make it possible,"
answers Nestor, who explains that profits from marketing the database
to companies can be funneled back into health care. The Estonian database
will be the property of a non-profit foundation formed by EGF and the
Ministry of Health who would create a body with rights to sell access
and information. Metspalu and others in the academic establishment hope
the database could also seriously boost Estonia's biomedical research
and kick-start the budding biotech sector. Access to data will be given
to local and outside public researchers freely or for a handling fee.

Just ten years after emerging as an independent nation after decades of
Soviet rule, the Estonians cannot go it alone. They are looking for outside
scientific collaboration and investments in the ballpark of $150 million
mainly to cover the massive and expensive genotyping effort. To spread the
word among scientists and investors the EGF held an international meeting
in Tartu on September 21-22, where practical, legal and ethical questions
involved were discussed. "It is important to be open about this and to make
sure all the relevant questions are asked and answered," says Pikani.